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Advanced anode materials with high theoretical capacity and rate capability are urgently required for next generation lithium ion batteries (LIBs). In this study, hierarchical N, P codoped porous 3D-carbon framework@TiO2 nanoparticle hybrid (N, P C@TiO2) is synthesized by using pollen as biomass precursor through a facile template assisted sol–gel methode and exhibits hierarchical porous hollow structure with plenty of redox active sites and enhanced specific surface area. Compared with N, P codoped porous micro-carbon sphere framework and TiO2 porous hollow microspheres anodes, the N, P C@TiO2 anode shows superior reversible capacity of 687.3 mAh g−1 at 0.1 A g−1 after 200 cycles and 440.5 mAh g−1 after 1000 cycles at 1 A g−1. The excellent performance can be attributed to the rational hierarchical porous hollow structure and the synergetic contributions from the N, P codoped-carbon and TiO2 components, which enhance Li+ storage capability, accelerate the reaction kinetics and stabilize the electrode structure and interface during charge/discharge process. This study suggests a practical strategy to prepare novel anode material with abundant natural resource and facile synthetic route, and the optimized hybrid anode with outstanding Li+ storage properties provides hopeful application prospect in advanced LIBs and other energy storage devices.

Photothermal therapy (PTT) has shown promising applications in tumor therapies. However, due to laser-induced nonspecific heating and heat diffusion, high levels of hyperthermia (>50°C) in tumor tissues often increase the risk of cancer recurrence and metastasis, which causes the patient pain and destroys the surrounding normal cells and tissues. It is therefore important to develop photothermal strategies that have excellent therapeutic efficiencies under low-temperature conditions (≤45°C). In addition, the heterogeneity and complexity of tumors require the development of combinatorial antitumor treatments as the therapeutic efficiency of monomodal PTT is not currently sufficient. Herein, we have adopted a stepwise synthetic approach to develop a highly efficient multimodal therapeutic agent GA@PCOF@PDA by successive bonding defect functionalization (BDF), guest encapsulation, and surface modification steps. The covalently grafted porphyrinic photosensitizers (Por), encapsulated gambogic acid (GA), and surface-modified PDA film are independently responsible for photodynamic therapy (PDT), heat-shock protein 90 (HSP90) down-regulation and chemotherapy (CT), and low-temperature PTT. This proof-of-concept study illustrates an efficient, generalized approach to design high-performance covalent organic framework (COF)-based nanoagents that can be easily tailored to combine different therapeutic modalities for improved cancer theranostics at low temperatures.

Hesperetin-7-O-glucoside (Hes-7-G) is a naturally occurring flavonoid monoglucoside in Citri Reticulatae Pericarpium and exhibits relatively high biological activities. To explore the anti-inflammatory capacity of dietary Hes-7-G, lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and dextran sodium sulfate (DSS)-induced colitis mice were used here as in vitro and in vivo inflammation models. The results showed that Hes-7-G (5 μM) significantly restored cellular metabolic disorders and inflammation in LPS-stimulated RAW264.7 macrophages. In the in vivo study, dietary Hes-7-G (1 mg/kg body weight) markedly alleviated the inflammatory status in DSS-induced colitis mice, manifested by the recovered colon length from 5.91 ± 0.66 to 6.45 ± 0.17 cm, histopathological changes, and mRNA levels of colonic inflammatory factors including Tnf-α and Il-22. Furthermore, dietary Hes-7-G not only profoundly regulated the gut microbiota composition including phyla Bacteroidetes, Cyanobacteria, Desulfobacterota, and Deferribacteres and genus Enterorhabdus, Prevotellaceae, Gastranaerophilales, Enterococcus, Intestinimonas, Ruminococcaceae, and Eubacterium in the cecal contents but also especially adjusted the co-metabolites such as short chain fatty acids and indole metabolites (indole-3-propionic, indole acetic acid), which were markedly altered by DSS treatment in mice. These findings demonstrated that Hes-7-G has strong anti-inflammatory activity in vitro and in vivo and potential preventive or therapeutic effects for chronic inflammation diseases.

A series of hydroxyl-terminated polyethylenes (HTPE) bearing various functional side groups (e.g. carboxyl, ester and butane groups) were synthesized by the combination of ring-opening metathesis polymerization (ROMP) and visible light photocatalytic thiol-ene reaction. The products are named as α, ω-dihydroxyl-poly[(propionyloxythio)methinetrimethylene] (HTPEcarboxyl), α, ω-dihydroxyl-poly[(methylpropionatethio) methinetrimethylene] (HTPEester) and α, ω-dihydroxyl-poly[(butylthio) methinetrimethylene] (HTPEbutane), respectively. The investigation of ROMP indicated that the molecular weight of resultant hydroxyl-terminated polybutadiene (HTPB) can be tailored by varying the feed ratios of monomer to chain transfer agent (CTA). The exploration of the photocatalytic thiol-ene reaction between HTPB precursor and methyl 3-mercaptopropionate revealed that blue light as well as oxygen accelerated the reaction. 1H-NMR and 13C-NMR results verified all the double bonds in HTPB can be modified, and the main chain of resultant polymer can be considered as polyethylene. Subsequently, relationship between the structure of side groups and the thermal properties of functional PEs was studied. And the results suggested that the Tg was in the order of HTPEbutane

Platinum is generally known as the most effective electrocatalyst for hydrogen evolution reaction because it can greatly lower the overpotential and accelerate the reaction kinetics, while its commercial potential always suffers from scarcity, high cost, low utilization, and poor durability particularly in acidic electrolytes. We herein demonstrate a facile method to improve the hydrogen evolution performance of Pt-based electrocatalysts by simply decorating the-state-of-the-art and commercially available Pt/C with hydrophobic protic ([DBU][NTf2]) or aprotic ([BMIm][NTf2]) ionic liquid. The current densities of [BMIm]@Pt/C and [DBU-H]@Pt/C with 10% ionic liquid at an overpotential of 40 mV are 2.81 and 4.15 times, respectively, higher than that of the pristine Pt/C. More importantly, ionic liquid-decoration significantly improves the long-term stability of Pt nanoparticles. After 8 h of chronoamperometric measurements, [DBU-H]@Pt/C and [BMIm]@Pt/C can still retain 83.7% and 78.3% of their original activity, respectively, which is much higher than that of the pristine Pt/C (24.4%). The improved performance of Pt/C decorated with ionic liquid is considered to arise from the improved proton conductivity (particularly for protic ionic liquid) and hydrophobic microenvironment created by the supported ionic liquid phase. The presence of ionic liquid layer not only de-coordinates H+ from hydronium ions nearby the Pt nanoparticles, but it also protects Pt nanoparticles from dissolution in the acidic media.

Lithium-sulfur (Li-S) battery with high theoretical energy density has been considered as an important energy storage system. However, its application has been limited by low cycling stability and rapid capacity decay due to the shuttle of lithium polysulfide (Li2Sn, n > 5). These problems can be solved using small sulfur molecules (S2–4) as the active material, while synthesis of carbon hosts with suitable pores size and narrow pore distribution to encapsulate small sulfur molecules are still challenging. Here, we report a novel nitrogen-doping microporous carbon (NDMC) sulfur host with narrow micropore unimodal size distribution centered at 0.57 nm. By accommodating small sulfur molecules (S2–4) within the subnanopores of NDMC, the formation and shuttle of soluble lithium polysulfide (LiPS) can be avoided. The cathode shows only a long potential plateau due to the direct conversion from S2–4 to Li2S. In carbonate-based electrolyte, the NDMC/S-2 cathode remains a stable and reversible capacity of 902 mAh g−1 at 0.2 C with 100% Coulombic efficiency after 500 cycles, and capacity fading per cycle is only around 0.02%. Besides, an excellent capacity of 511.8 mAh g−1 is achieved even at an ultrahigh rate of 10 C, demonstrating a superior rate capability performance. This NDMC/S composite also shows excellent cycling stability in ether-based electrolyte. All the above demonstrate the NDMC has great potential application in Li-S batteries.

Diatoms are unicellular organisms, and their cell walls (diatom frustules) composed of hydrated amorphous silica have the characteristic of a delicate porous structure. Herein, we explore the appli...

Carbon nano-onions (CNOs), as one of the allotropes of carbon, have attracted great attention because of their excellent performance in many fields, especially in capacitors. Developing soft-chemistry synthesis methods is critically of importance, while the forming mechanism in this area is not clear. In this paper, we present a critical review of CNOs regarding the structure, especially interlayer spacing, and synthesis processes, elaborating the recent progress on soft-chemistry methods. Hansen solubility parameter theory is applied to predict and regulate the solubility of CNOs. This article would be inspirational and give new insights into understanding the formation and properties of CNOs.

Background Scalp combing, as an ancient method of health care, has been used for thousands of years in traditional Chinese medicine. Although this method is considered to be beneficial for the blood circulation of the head, the underlying mechanisms remain unclear. Methods Both human participants and mice were used in this study. In participants, the scalp was stimulated by combing continuously for 5 min, and the temperature was measured using infrared thermal imaging before and after stimulation. In mice, the temperature was determined before and at 5, 15, and 30 min after a 5-min scalp mechanical stimulation (SMS). Additionally, the vasculature of the mice was labeled with retro-orbital fluorescein isothiocyanate-dextran injection, and the capillaries were observed directly under a confocal microscope. Using in vivo CLARITY imaging and the spectrofluorometric detection of Evans Blue dye extravasation, the blood–brain barrier permeability was assessed. Results SMS increased the temperature of the left ear significantly in human (P = .0247) while can slightly increase the temperature of the right ear and the face without significant difference (P > .05). Moreover, SMS can significantly slow the decrease in the temperature of the external auditory canal at 5 min (P = .0153) and in body temperature at 15 min (P = .0295) after SMS whereas no significant difference in body temperature at 30 min (P > .05) compared with control mice. Furthermore, capillaries of the ear with a diameter of less than 8 μm were significantly dilated (P = .0006) following SMS and the number of dextran dots was higher at 15 min (P > .05) and 30 min (F = 10.98, P = .037) after SMS intervention compared with control mice. Conclusion Our study provides strong evidence to support the notion that scalp combing can improve extra- and intracranial blood circulation under healthy conditions.

AIM: To compare the safety and efficacy of the intravitreal injection of conbercept (IVC) and triamcinolone acetonide (IVTA) for macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: A prospective, randomized clinical study. Patients with ME secondary to BRVO were randomly assigned to either IVC group or IVTA group at a ratio of 2:1 and a 12-month follow-up was performed. The efficacy outcome measures included the mean changes and differences in best corrected visual acuity (BCVA) and the central retinal thickness (CRT). The safety profiles and the mean retreatment intervals were also compared. RESULTS: There was no statistically significant difference of baseline between the two groups (IVC group, n=36; IVTA group, n=17). At 12mo, the BCVA letters improved by 27.31±18.36 in the IVC group, and 13.53±11.37 in the IVTA group (P=0.0004). CRT reduction was 253.33±163.69 and 150.24±134.32 µm, respectively (P=0.0034). The mean BCVA in the IVC group was superior to that of the IVTA group for months 6-12 (P

Carbon nano-onions with concentric fullerene-like carbon shells were synthesized by hydrothermal carbonization of citric acids at 180 °C and formed through the intermediates of graphene quantum dots, graphitic nano-sheets and graphitic hollow polyhedrons. The graphene quantum dots were firstly formed by the dehydration of citric acids and then grew and stacked into graphitic nano-sheets, which curved into graphitic hollow polyhedrons due to the interface energy. The graphitic hollow polyhedrons eventually transformed into spherical carbon nano-onions with the lowest interface energy in the hydrothermal solution by disordering and rearrangement of the carbon shell.

The challenge of enhancing the high-temperature oxidation resistance of TiAl alloys is hereby addressed by Co addition. Isothermal oxidation tests were conducted on the newly designed TiAl-Co alloys in laboratory air at 900 °C up to 100 h. Sintered microstructure, oxidation kinetics, scale structure, spallation resistance and oxidation mechanisms were systematically investigated. Results show that the original sintered microstructure of TiAl alloys mainly consists of matrix phases α2-Ti3Al/γ-TiAl lamellae, while the Co addition leads to the formation of the two additional Co-rich phases of CoAl2Ti and Ti (Al, Co, Cr and Nb) at grain boundaries. The Co-doped TiAl alloys exhibit an improved high-temperature oxidation resistance compared with the Co-free alloy. The presence of the Co-rich phases network along the grain boundaries and Co-rich layer at the scale/substrate interface can hinder the inward diffusion of oxygen and the outward diffusion of Ti and Al, thereby suppressing the growth of oxide scale and improving the spallation resistance of TiAl alloys. As a result, the TiAl-3Co alloy possesses excellent oxidation resistance, with the minimum mass gain of 4.08 mg/cm2, thinnest scale thickness of 17.8 μm and without surface spallation or crack formation after isothermal oxidation for 100 h. This result would pave the way for designing high-temperature oxidation-resistant TiAl-based alloys.

Brain matrix metalloproteinases (MMPs) have been recently implicated in alcohol addiction; however, the molecular mechanisms remain poorly understood. Matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease, is the best described MMP that is thought to regulate addictive behavior. In the present study, the effect of MMP-9 overexpression on hippocampal neuron plasticity and alcoholic behavior was assessed in spontaneous alcohol drinking mice. Two-bottle choice model showed that the overexpression of MMP-9 in the hippocampus developed by adeno-associated virus (AAV) could decrease alcohol consumption and preference, but did not affect taste preference, which was tested using saccharin or quinine solutions. Dendritic spines number of hippocampal neurons was observed by Golgi staining. Compared with the alcohol treatment group, the density of dendritic spines in the hippocampus of alcohol drinking mice was decreased in alcohol + MMP-9 group. Western blot analysis indicated that GluN1 expression in the hippocampus of alcohol drinking group was lower than that in the control group, while the expression of GluN1 was increased in MMP-9 overexpressing mice. MMP-9 also regulated the depolymerization of actin filaments, which induced behavioral changes in mice. Taken together, overexpression of MMP-9 in the hippocampal neurons of mice resulted in decreased dendritic spine density and F-actin/G-actin ratio, which might be the crucial reason for the significant decrease in alcohol consumption in alcohol drinking mice. MMP-9 might be considered as a novel target studying the molecular mechanism of alcohol drinking.

Silent Information Regulator 1 (SIRT1), an NAD+-dependent deacetylase, contributes to the neuroprotective effect. However, intracellular signaling pathways that affect SIRT1 function remain unknown. It is well known that N-methyl-D-aspartate (NMDA) receptor activation induces calcium influx which then activates PKC, and SIRT1 is a mRNA target for HuR protein. We hypothesize that Ca2+-PKC-HuR-SIRT1 pathway modulates SIRT1 function. The present study is to investigate the potential pathway of SIRT1 in the SH-SY5Y cell line as an in vitro model of NMDA-induced neurotoxicity. The results showed that: (1) SIRT1 levels were downregulated in NMDA model; (2) NMDA induced an increase in serine phosphorylation of HuR, while inhibition of serine phosphorylation of HuR increased SIRT1 levels, promoting cell survival; (3) PKC inhibitor (Go 6976) reversed NMDA insults and also suppressed serine phosphorylation of HuR; (4) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator, fully reversed NMDA insults and also inhibited PKC activity evoked by NMDA. These results indicate that intracellular elevated Ca2+ activates PKC, which phosphorylates HuR and then promotes SIRT1 mRNA decay and subsequent neuronal death in NMDA model. Therefore, the study suggests that inhibition of Ca2+-PKC-HuR-SIRT1 pathway could be an effective strategy for preventing certain neurological diseases related to NMDA excitotoxicity.

Long-term continuous oxygen supply is of vital importance during the process of space exploration. Considering the cost and feasibility, in situ resource utilization (ISRU) may be a promising solution. The conversion of CO2 to O2 is a key point for ISRU. In addition, the utilization of the abundant CO2 resources in the atmosphere of Mars is an important topic in the field of manned deep space exploration. The Sabatier reaction, Bosch reaction, and solid oxide electrolysis (SOE) are well-known techniques for the reduction of CO2. However, all the above techniques need great energy consumption. In this article, we designed an electrochemical membrane reactor at room temperature based on microfluidic control for the reduction of CO2 in extraterrestrial space. In this system, H2O was oxidized to O2 on the anode, while CO2 was reduced to C2H4 on the cathode. The highest Faraday efficiency (FE) for C2H4 was 72.7%, with a single-pass carbon efficiency toward C2H4 (SPCE-C2H4) of 4.64%. In addition, a microfluidic control technique was adopted to overcome the influence of the microgravity environment. The study may provide a solution for the long-term continuous oxygen supply during the process of space exploration.

Dopamine (DA) is a crucial neurotransmitter that plays an important role in maintaining physiological function in human body. In the past, most studies focused on the relationship between the dopaminergic system and neurological-related diseases. However, it has been found recently that DA is an immunomodulatory mediator and many immune cells express dopamine receptors (DRs). Some immune cells can synthesize and secrete DA and then participate in regulating immune function. DRs agonists or antagonists can improve the dysfunction of immune system through classical G protein signaling pathways or other non-receptor-dependent pathways. This article will discuss the relationship between the dopaminergic system and the immune system. It will also review the use of DRs agonists or antagonists to treat chronic and acute inflammatory diseases and corresponding immunomodulatory mechanisms.

The transition of amyloidogenic species into ordered structures (i.e., prefibrillar oligomers, protofibrils, mature fibrils, and amyloidogenic aggregates) is closely associated with many neurodegenerative disease pathologies. It is increasingly appreciated that the liquid-solid interface contributes to peptide aggregation under physiological conditions. However, much remains to be explored on the molecular mechanism of surface-directed amyloid formation. We herein demonstrate that physical environmental conditions (i.e., negatively charged surface) affect amyloid formation. Nontoxic amyloid aggregates quickly develop into intertwisting fibrils on a negatively charged mica surface. These fibrillar structures show significant cytotoxicity on both neuroblastoma cell-lines (SH-SY5Y) and primary neural stem cells. Our results suggest an alternative amyloid development pathway, following which A beta peptides form large amyloidogenic aggregates upon stimulation, and later transit into neurotoxic fibrillar structures while being trapped and aligned by a negatively charged surface. Conceivably, the interplay between chemical and physical environmental conditions plays important roles in the development of neurodegenerative diseases.

Anhydrosafflor Yellow B (AHSYB), is an effective ingredient with a high content extracted from safflower. The effect of hydroxysafflor yellow A (HSYA), one of the main compounds in safflower, has b...

Forebrain ischemia induces delayed, selective neuronal death in hippocampal CA1. It has been established that BDNF (brain-derived neurotrophic factor) is an important factor in ischemic injury. However, the exact mechanism of BDNF expression in the hippocampus after ischemia is unclear. We found that the decrease of BDNF protein expression in hippocampal CA1 was associated with a decrease of Bdnf transcript IV expression in the same region of the rats after ischemia/reperfusion (I/R). In hippocampal CA3 and DG, the results showed increased expression of BDNF protein and transcripts I, IIc, III, IV, VI, and X1. Furthermore, at the Bdnf promoters, I/R led to decreased H3K27ac, increased H3K9ac, and H3K14ac in CA1; increased H3K9ac, H3K14ac, and H3K27ac in CA3; no significant change of H3K9ac, H3K14ac, and H3K27ac in DG. HDAC inhibitor SAHA increased the expression of Bdnf transcripts IV, VI, and X1 in CA1. These findings suggest a potential of modulation Bdnf transcript expression to resolve ischemic brain injury through histone acetylation patterns at the Bdnf promoters.

Amorphous materials have low mobility due to their nature of disorder. Surprisingly, some disordered materials showed photocurrent amplification not by conventional photoconductive gain. Recently, amorphous Silicon (a-Si) photodiodes with thin a-Si layer (∼40 nm) have shown a gain-bandwidth product of over 2 THz with very low excess noise and also have been used as a gain media in a cascaded system with single photon sensitivity. To unveil the true gain mechanism, we performed theoretical modeling and numerical analysis along with experimental data at different frequencies. We show evidence of highly effective carrier multiplication process within a-Si as the primary gain mechanism, especially at high frequency. We also show presence of trap-induced junction modulation at much lower frequency. We modeled the gain mechanism in a-Si by solving the transport equations including dynamics of defect states and carrier multiplication via the local field model. We further justified the application of local field model for thin a-Si, based on the property that in a-Si, the mean-free path for energy relaxation is orders of magnitude greater than the mean-free-path for momentum relaxation. The analysis further suggests that the carrier multiplication process in thin a-Si can be much more efficient than in thick a-Si, even stronger than single crystalline Si in some cases. Although seemingly counter intuitive, this is consistent with the proposed cycling excitation process where the localized states in the bandtails of disordered materials such as a-Si relax the k -selection rule and increase the rate of carrier multiplication.

Photodetectors made of amorphous materials enable low-cost optical imaging and communications over non-semiconductor platforms. The key challenges are to improve efficiency, sensitivity, and frequency response. Using the localized surface plasmon resonance (LSPR) effect and an efficient carrier multiplication process, cycling excitation process (CEP), the plasmonically enhanced amorphous silicon photodetector (PEASP) with a thin (60 nm) absorption layer achieves a high external quantum efficiency with a record fast impulse response of 170 ps (FWHM). This approach offers the possibility of making detectors out of amorphous material for high frame rate imaging and optical communications in spite of the material’s low carrier mobility.

The ultrasonication-triggered interfacial assembly approach was developed to synthesize magnetic Janus amphiphilic nanoparticles (MJANPs) for cancer theranostic applications, where the biocompatible octadecylamine is used as a molecular linker to mediate the interactions between hydrophobic and hydrophilic nanoparticles across the oil-water interface. The obtained Co cluster-embedded Fe3O4 nanoparticles-graphene oxide (CCIO-GO) MJANPs exhibited superior magnetic heating efficiency and transverse relaxivity, 64 and 4 times higher than that of commercial superparamagnetic iron oxides, respectively. The methodology has been applicable to nanoparticles of various dimensions (5-100 nm), morphologies (sphere, ring, disk, and rod), and composition (metal oxides, noble metal and semiconductor compounds, etc.), thereby greatly enriching the array of MJANPs. In vivo theranostic applications using the tumor-bearing mice model further demonstrated the effectiveness of these MJANPs in high-resolution multimodality imaging and high-efficiency cancer therapeutics. The ubiquitous assembly approach developed in the current study pave the way for on-demand design of high-performance Janus amphiphilic nanoparticles for various clinical diagnoses and therapeutic applications.

Effective delivery of anticancer drugs into the nucleus for pharmacological action is impeded by a series of intratumoral transport barriers. Despite the significant potential of magnetic nanovehicles in electromagnetic field (EF)‐activated drug delivery, modularizing a tandem magnetoresponsive activity in a one‐nanoparticle system to meet different requirements at both tissue and cellular levels remain highly challenging. Herein, a strategy is described by employing sequential EF frequencies in inducing a succession of magnetoresponses in the magnetic nanovehicles that aims to realize cascaded tissue penetration and nuclear accumulation. This nanovehicle features ferrimagnetic vortex‐domain iron oxide nanorings coated with a thermo‐responsive polyethylenimine copolymer (PI/FVIOs). It is shown that the programmed cascading of low frequency (Lf)‐EF‐induced magnetophoresis and medium frequency (Mf)‐EF‐stimulated magneto‐thermia can steer the Doxorubicin (DOX)‐PI/FVIOs to the deep tissue and subsequently trigger intracellular burst release of DOX for successful nuclear entry. By programming the order of different EF frequencies, it is demonstrated that first‐stage Lf‐EF and subsequent Mf‐EF operation enables DOX‐PI/FVIOs to effectively deliver 86.2% drug into the nucleus in vivo. This nanodelivery system empowers potent antitumoral activity in various models of intractable tumors, including DOX‐resistant MCF‐7 breast cancer cells, triple‐negative MDA‐MB‐231 breast cancer cells, and BxPC‐3 pancreatic cancer cells with poor permeability., A magnetic nano‐delivery system is developed to achieve drug nuclear delivery in vivo for efficient cancer therapy. By programming the order of different electromagnetic field (EF) frequencies, the first‐stage low frequency‐EF‐induced magnetophoresis and subsequent medium frequency ‐EF‐stimulated magneto‐thermia, enables drug‐carrying magnetic vortex nanorings to realize cascaded tissue penetration and drug nuclear accumulation in vivo. This nanodelivery system empowers potent antitumoral activity.

Vibrio alginolyticus is a common opportunistic pathogen that can cause vibriosis of marine aquatic animals. The application of phages or particularly associated protein products for the treatment of vibriosis has shown prominent advantages compared with the treatment with traditional antibiotics. In this study, the function of a holin-endolysin system from V. alginolyticus phage HH109 was characterized by examining the effect of their overexpression on Escherichia coli and V. alginolyticus. Our data revealed that the endolysin of the phage HH109 has stronger bactericidal activity than the holin, as evidenced by observing more cell death and severe structural damage of cells in the endolysin-expressing E. coli. Furthermore, the two proteins displayed the synergistic effect when the holA and lysin were co-expressed in E. coli, although no interaction between them was detected using the bacterial two-hybrid assay. Transmission electron microscopy observation revealed disruptions of cell envelopes accompanied by leakage of intracellular contents. Similarly, the bactericidal activity of the holin and endolysin against V. alginolyticus was also examined whatever the host is sensitive or resistant to phage HH109. Together, our study contributes to a better understanding of the mechanism of phage HH109 destroying the bacterial cell wall to lyse their host and may offer alternative applications potentially for vibriosis treatment.

Summary Collective behavior emerges in diverse life machineries, e.g., the immune responses to dynamic stimulations. The essential questions that arise here are that whether and how cells in vivo collectively respond to stimulation frequencies higher than their intrinsic natural values, e.g., the acute inflammation conditions. In this work, we systematically studied morphological and signaling responses of population fibroblasts in an interconnected cell monolayer and uncovered that, besides the natural NF-κB oscillation frequency of 1/90 min−1, collective signaling response emerges in the cell monolayer at 1/20 min−1 TNF-α input periodicity as well. Using a customized microfluidic device, we independently induced dynamic chemical stimulation and cytoskeleton reorganization on the stand-alone cells to exclude the effect of cell-cell communication. Our results reveal that, at this particular frequency, chemical stimulation is translated into dynamic intracellular mechanical cues through RAC1-medicated induction of dynamic cell-cell connections and cytoskeleton reorganizations, which synergize with chemical input to facilitate collective signaling responses., Graphical abstract, Highlights • Dynamic intracellular mechanical cues facilitate collective cellular responses • The dynamic chemical stimulations are translated into intracellular mechanical cues • The synergy between dynamic mechanical and chemical signal plays crucial roles, Mechanobiology; Cellular Physiology; Cell Biology

Mimicking in vivo environmental conditions is crucial for in vitro studies on complex life machinery. However, current techniques targeting live cells and organs are either highly expensive, like robotics, or lack nanoliter volume and millisecond time accuracy in liquid manipulation. We herein present the design and fabrication of a microfluidic system, which consists of 1,500 culture units, an array of enhanced peristaltic pumps and an on-site mixing modulus. To demonstrate the capacities of the microfluidic device, neural stem cell (NSC) spheres are maintained in the proposed system. We observed that when the NSC sphere is exposed to CXCL in day 1 and EGF in day 2, the round-shaped conformation is well maintained. Variation in the input order of 6 drugs causes morphological changes to the NSC sphere and the expression level representative marker for NSC stemness (i.e., Hes5 and Dcx). These results indicate that dynamic and complex environmental conditions have great effects on NSC differentiation and self-renewal, and the proposed microfluidic device is a suitable platform for high throughput studies on the complex life machinery.

Problem During the first trimester, the accumulation of macrophages, which is the second largest decidual leukocyte population (~20%) at the maternal-fetal interface, is quite vital for a successful pregnancy, including embryo implantation, trophoblast invasion, and vascular remodeling. The mechanism of the enrichment and redistribution of macrophages in the uterine decidua of early pregnancy is largely unclear. Method of study A total of 37 women with normal early pregnancies were included. Primary decidual macrophages (dMφs) (n = 37) and primary decidual stromal cells (DSCs) (n = 37) were isolated, and the adhesion molecules were analyzed by flow cytometry (FCM). Adhesive experiment was carried out to evaluate the adhesion capacity by counting cell numbers of dMφs adhered to DSCs in a co-culture system. Results We found that RANK+ dMφs was the dominating subtype at the maternal-fetal interface. The expression of adhesion molecules (eg, CD29, CD31, CD54, and CD62L) on the surface of RANK+ dMφs was higher than that of RANK- dMφs. After co-culture with DSCs, the expression of adhesion molecules on dMφs was up-regulated in a RANKL-dependent manner. Meanwhile, dMφs promoted the releasing of RANKL on DSCs after co-culture. Consistently, dMφs exhibited the lessoned capacity of adhesion to DSCs when blocking the crosstalk of RANKL-RANK between the DSCs and dMφs in vitro. Conclusion These results suggest that the interaction of RANKL-RANK up-regulates the expression of adhesion molecules on the surface of dMφs, contributing to the accumulation and residence of dMφs in human early pregnancy.

In this study, healthy Wuchang bream (Megalobrama amblycephala) juveniles were exposed to 0, 5, 10, 20 and 30 mg/L total ammonia nitrogen for 30 days to elucidate toxic effects and mechanisms of ammonia on growth performance involved with the regulation of growth hormone/insulin-like growth factor (GH/IGF) and hypothalamic-pituitary-thyroid (HPT) axes. Our results showed that the increasing total ammonia nitrogen concentrations caused dose-depend decreases in the weight gain and specific growth rate but increases in the food conversion ratio and mortality in juvenile bream, indicating growth inhibitory effects induced by ammonia. Concurrently, GH, IGF-1 at protein and mRNA levels were significantly decreased in ammonia exposure groups (p < .05), while serum thyroid stimulating hormone, free thyroxine, free triiodothyronine levels were significantly reduced only in fish exposed to higher concentrations of 20 and 30 mg/L ammonia (p < .05), suggesting that ammonia exposure could perturb both GH/IGF-axis and HPT-axis functions. Furthermore, transcriptional levels of extracellular regulated protein kinases 2 (erk2), phosphatidylinositol 3-kinase (pi3k), protein kinase B (akt), target of rapamycin (tom) and ribosomal protein S6 kinase-polypeptide 1(s6k1) in the dorsal muscle were significantly down-regulated in the fish exposed to ammonia (p < .05). This fact indicated that MAPK/ERK pathway and PI3K/AKT pathway should be responsible for the growth inhibition. Combining the results of spearman correlation coefficient, it should be noted that the GH/IGF axis played a more important role in regulating the growth than the HPT axis in Wuchang bream under persistent ammonia stress.

In this work, a novel amphoteric copolymer named Poly(sodium p-styrenesulfonate– co -acrylic acid- co -diallyldimethylammonium chloride) (P(SS- co -AA- co -DMDAAC)) was synthesized via free radical polymerization. Afterwards, P(SS- co -AA- co -DMDAAC) was explored for use as a dispersant in coal water slurry (CWS) preparation. The structure of P(SS- co -AA- co -DMDAAC) was verified by Fourier transform infrared spectroscopy and nuclear magnetic resonance. The synthetic conditions were optimized as the feed ratio of AA to SS was 1 : 1 (for Yulin coal) or 1.5 : 1 (for Yili coal), and DMDAAC dosage was 4.0 wt% (for Yulin coal) and 6.0 wt% (for Yili coal) toward total monomers. The performances of P(SS- co -AA- co -DMDAAC) as a dispersant for CWS were evaluated by various technologies, such as apparent viscosity, zeta potential, static stability and contact angle measurements. The results revealed that the optimized dosage of P(SS- co -AA- co -DMDAAC) in CWS preparation was 0.3 and 0.4 wt% for Yulin coal and Yili coal respectively. In this optimum condition, CWS prepared using P(SS- co -AA- co -DMDAAC) as dispersant showed a typical shear thinning behaviour and excellent stability, which are desired in industries. The rheological models also confirmed the pseudo-plastic characteristics of CWS. Finally, compared with the widely used anionic dispersant naphthalene sulphonate formaldehyde condensate (NSF) and poly(sodium p-styrenesulfonate) (PSS), P(SS- co -AA- co -DMDAAC) developed in this work exhibited better slurry making performance. The introduction of cationic functional groups promoted the adsorption of the dispersant, which further enhanced the electrostatic repulsion and steric hindrance among coal particles. Accordingly, the viscosity of CWS decreased and static stability enhanced.

Selective protein distribution on distinct plasma membranes is important for epithelial cell function. To date, how proteins are directed to specific epithelial cell surface is not fully understood. Here we report a conserved DSSDE motif in LDL-receptor (LDLR) modules of corin (a transmembrane serine protease) and CD320 (a receptor for vitamin B12 uptake), which regulates apical membrane targeting in renal epithelial cells. Altering this motif prevents specific apical corin and CD320 expression in polarized Madin–Darby canine kidney (MDCK) cells. Mechanistic studies indicate that this DSSDE motif participates in a Rab11a-dependent mechanism that specifies apical sorting. In MDCK cells, inhibition of Rab11a, but not Rab11b, expression leads to corin and CD320 expression on both apical and basolateral membranes. Together, our results reveal a novel molecular recognition mechanism that regulates LDLR module-containing proteins in their specific apical expression in polarized renal epithelial cells.

Matrix metalloproteinase-9 (MMP-9, Gelatinase B), an extracellular-acting Zn2+-dependent endopeptidase, are involved in brain pathologies including ischemia, glioma, and epilepsy. Recent studies suggested that MMP-9 plays an important role in neuronal plasticity, specifically in learning and memory. To determine whether and how MMP-9 plays role in alcohol-related behaviors, male Sprague–Dawley (SD) rats were subjected to chronic intermittent ethanol (CIE) exposure for 4 weeks, following which we collected tissue samples from the hippocampus, medial prefrontal cortex (mPFC), and amygdala at different stages (acute and chronic exposure) during alcohol exposure. Real-time PCR and western blot assays were used to detect changes in the mRNA and protein expression of MMP-9. Our results indicated that both acute and chronic alcohol exposure induced up-regulation of MMP-9 mRNA levels in the hippocampus and mPFC, but not in the amygdala. Furthermore, acute and chronic alcohol exposure up regulated the expression of total MMP-9 and active MMP-9 in these two brain regions. Moreover, the increase of active MMP-9 expression was larger than those in total MMP-9 expression. Immunoprecipitation analyses identified potential MMP-9-interacting proteins, including Itgb1, Src, Eef1a2, tubulin, actin, and histone H2B. These results demonstrate that both acute and CIE exposure induced increases in MMP-9 expression in the mPFC and hippocampus, suggesting that MMP-9 plays a key role in chronic alcohol exposure and dependence.

Significance Physiological regulation and behavior depend less on neurons than on neuronal circuits. Neurosignal integration is the basis of neurocircuit function. The modalities of neuroinformation integration are evolutionarily conserved in animals and humans. Here, we identified two modalities of neurosignal integration in two different circuits by which serotonergic ADFs regulate pharyngeal pumping in Caenorhabditis elegans: disinhibition in a feedforward circuit consisting of ADF, RIC, and SIA neurons and disexcitation, a modality of neurosignal integration suggested by this study, in a feedback circuit consisting of ADF, RIC, AWB, and ADF neurons., Feeding is vital for animal survival and is tightly regulated by the endocrine and nervous systems. To study the mechanisms of humoral regulation of feeding behavior, we investigated serotonin (5-HT) and octopamine (OA) signaling in Caenorhabditis elegans, which uses pharyngeal pumping to ingest bacteria into the gut. We reveal that a cross-modulation mechanism between 5-HT and OA, which convey feeding and fasting signals, respectively, mainly functions in regulating the pumping and secretion of both neuromodulators via ADF/RIC/SIA feedforward neurocircuit (consisting of ADF, RIC, and SIA neurons) and ADF/RIC/AWB/ADF feedback neurocircuit (consisting of ADF, RIC, AWB, and ADF neurons) under conditions of food supply and food deprivation, respectively. Food supply stimulates food-sensing ADFs to release more 5-HT, which augments pumping via inhibiting OA secretion by RIC interneurons and, thus, alleviates pumping suppression by OA-activated SIA interneurons/motoneurons. In contrast, nutrient deprivation stimulates RICs to secrete OA, which suppresses pumping via activating SIAs and maintains basal pumping and 5-HT production activity through excitation of ADFs relayed by AWB sensory neurons. Notably, the feedforward and feedback circuits employ distinct modalities of neurosignal integration, namely, disinhibition and disexcitation, respectively.

Most chemotherapeutic drugs commonly suffer from low aqueous solubility that can potentially limit drugs absorption. Drug nanomerization is an advanced approach to overcoming their poor water-solubility. In this study, class I hydrophobin recombinant HGFI (rHGFI)-based curcumin (Cur) nanoparticles (rHGFI-Cur) were prepared by freeze-drying method. The rHGFI-Cur nanocomposites were characterized by contact angle, transmission electron microscopy, fluorescence microscopy and dynamic light scattering. The results showed that rHGFI could lead to the wettability conversion and stability improved of Cur in water. X-ray photoelectron spectroscopy and Fourier transform infrared suggested that rHGFI could non-covalently bind to Cur to render them hydrophilic through hydrophobic forces. Additionally, drug release and cytotoxicity assays illustrated that rHGFI-Cur nanoparticles could facilitate Cur release and exhibited higher cytotoxicity than free Cur for human esophageal cancer cells TE-1. Thus, it suggested that rHGFI has a great potential application for hydrophobic drug delivery without toxicity.[Formula: see text].

Type II transmembrane serine proteases (TTSPs) are a group of enzymes participating in diverse biological processes. Some members of the TTSP family are implicated in viral infection. TMPRSS11A is a TTSP expressed on the surface of airway epithelial cells, which has been shown to cleave and activate spike proteins of the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome coronaviruses (CoVs). In this study, we examined the mechanism underlying the activation cleavage of TMPRSS11A that converts the one-chain zymogen to a two-chain enzyme. By expression in human embryonic kidney 293, esophageal EC9706, and lung epithelial A549 and 16HBE cells, Western blotting, and site-directed mutagenesis, we found that the activation cleavage of human TMPRSS11A was mediated by autocatalysis. Moreover, we found that TMPRSS11A activation cleavage occurred before the protein reached the cell surface, as indicated by studies with trypsin digestion to remove cell surface proteins, treatment with cell organelle-disturbing agents to block intracellular protein trafficking, and analysis of a soluble form of TMPRSS11A without the transmembrane domain. We also showed that TMPRSS11A was able to cleave the SARS-CoV-2 spike protein. These results reveal an intracellular autocleavage mechanism in TMPRSS11A zymogen activation, which differs from the extracellular zymogen activation reported in other TTSPs. These findings provide new insights into the diverse mechanisms in regulating TTSP activation.

Mitochondria-targeting nanotherapy receives great attention these days for its capacity in disrupting mitochondria function and inducing tumor cell apoptosis through external magnetic and optical stimulations. However, the effect is significantly diminished when applied to animal models. The key factors include environmental complexity in vivo and intrinsic protective features of tumor tissues. To address these obstacles and reduce expenses on drug screening, we herein introduce a methodology for producing millimeter-sized spheroids with structural and functional characteristics of tumor tissues in vivo. The necessity of spheroid as a liver tumor model is demonstrated by comparing the effect of TPP-SPIONs (triphenylphosphonium cation-superparamagnetic iron oxide nanoparticles) on monolayer-cultured HepG2 cells and spheroids. Our study reveals that large-scale spheroid, in contrast to monolayer cells, reflects more in vivo tumor characters and is less responsive to TPP-SPIONs during magnetic hyperthermia treatment.

Dark-field microscopy directly detects scattered light from a sample, and therefore requires no fluorescent labeling for single molecule detection. The technique has been extensively used for spectral characterization of nanoscopic particles, but its sensitivity to variations in molecular density has not been explored. 3D chromosome topology plays important roles in regulating life processes. Physical characteristics of DNA (e.g. persistence length) and its interaction with numerous proteins and polyamines determine chromosome and chromatin 3D topology. We herein demonstrate the capacity of dark-field microscopy in real-time monitoring of single DNA molecules' conformation and dynamics. Without fluorescent staining, DNA molecules remain intact in physical characteristics like persistence length, net charges and width of the chain. Exclusion of photobleaching and photocleavage effects allows long-term imaging of bare DNA chains at high ionic strength, in shear flows and in the presence of condensing and stretching agents. Furthermore, our studies reveal that the brightness of single molecules during dark-field imaging is determined by DNA conformation, dark when being stretched and bright upon condensation. The sensitivity of dark-field microscopy to nonuniform distribution of molecular density allows us to study the dynamic activities of the transcriptional factor within the cell membrane. In contrast to a fluorescently tagged antibody, which binds to a specific signaling pathway, variations in molecular density across the nuclear envelope can better represent cellular responses upon stimulation.

The group A scavenger receptor cysteine-rich (SRCR) domain is a conserved module present in numerous proteins involved in diverse biological processes. Hepsin, a hepatic protease implicated in many cancers, consists of a cytoplasmic tail, a transmembrane domain and an extracellular regions with a group A SRCR domain and a serine protease domain. Like in many SRCR-containing proteins, the SRCR domain in hepsin has an N-glycosylation site, but its functional significance is unknown. In this study, we confirmed N-glycosylation at Asn112 in hepsin by glycosidase digestion and site-directed mutagenesis in human hepatoma cells. In Western blotting, fluorogenic substrate assay, flow cytometry, and protein-chase experiments, we found that Asn112 to Gln (N112Q) mutation inhibited hepsin intracellular trafficking, cell surface expression, and zymogen activation. By immunofluorescent staining, we found that the N112Q mutant was more abundant than wild-type hepsin in the endoplasmic reticulum (ER). Further co-immunoprecipitation studies indicated increased binding of the N112Q mutant to calnexin and binding-immunoglobulin protein (BiP), two ER chaperones. Our results indicate that the N-glycan in the SRCR domain of hepsin promotes intracellular trafficking and cell surface expression, possibly by a calnexin-dependent mechanism in facilitating ER exiting.